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An evolutionarily acquired microRNA cluster shapes development of mammalian cortical projections

Award Number: R01NS134969
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2028

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An evolutionarily acquired microRNA cluster shapes development of mammalian cortical projections - Project Summary The mammalian central nervous system contains unique projections from the cerebral cortex thought to underpin complex motor and cognitive skills. These projections include the corticospinal tract. involved in motor function, and the corpus callosum, involved in executive function. The cerebral cortical neurons that give rise to the corticospinal tract and corpus callosum are, respectively, corticospinal motor neurons and callosal projection neurons. These neurons develop from the same progenitor pool at the same time in development, but they acquire strikingly different projections to serve strikingly different behaviors. The mechanisms whereby corticospinal and callosal projection neurons develop represents a fundamental open question in basic neuroscience: how do the unique projections underlying complex mammalian behaviors arise? While it is known that transcription factors play a critical role in the fate of corticospinal, callosal, and other cortical projection neurons, the contribution of other gene regulatory mechanisms is poorly understood. We posit that a genomic cluster of selectively expressed microRNAs are epigenetically co-regulated in corticospinal motor neurons (Aim 1 ), where they in turn co-regulate axon guidance pathways (Aim 2) to favor corticospinal over callosal projection neuron fate (Aim 3). We will employ deep sequencing and in vivo functional perturbation studies to test our hypothesis. This microRNA-mediated specification of fate represents a novel mechanism of cortical projection neuron development, with implications not only for fundamental mechanisms of cortical development, but also for understanding the evolution of the complex connectivity of the mammalian central nervous system.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $352,621 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	12/12/2025	NON-COMPETING CONTINUATION	$352,621
														Subtotal = $352,621

Issue Date FY: 2025 ( Subtotal = $353,483 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/13/2025	NON-COMPETING CONTINUATION	$353,483
														Subtotal = $353,483

Issue Date FY: 2024 ( Subtotal = $392,561 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	11/27/2023	NEW	$392,561
														Subtotal = $392,561

Grand Total All Awards = $1,098,665

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An evolutionarily acquired microRNA cluster shapes development of mammalian cortical projections

Award Number: R01NS134969

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/01/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2028

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